Factor VIII is the plasma protein which is functionally deficient in hemophilia A patients, resulting in the clinical bleeding disorder. Patients with this disease require frequent infusions of Factor VIII in order to maintain hemostasis, particularly during surgery or following physical trauma. Presently, the commercial Factor VIII product is purified from pooled blood plasma obtained from human donors. Recent developments have made it possible to produce commercially viable amounts of Factor VIII using recombinant host/vector systems. The product from such a production scheme should have substantially improved properties relative to the plasma-derived product. These include higher purity, lower volumes and markedly reduced risk of viral contamina- tion. Recent experiments have indicated that the Factor VIII molecule can be extensively modified by techniques of molecular genetics and retain its in vitro and in vivo activity. The aim of the proposed research plan is to genetically modify the Factor VIII protein to further improve its pharmacologic utility while reducing the cost of treatment using recombinant DNA technologies.